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    GENE:

    MSH6 (MutS homolog 6)

    i
    Other names: MSH6, GTBP, MutS homolog 6
    1d
    Haplotype analysis detects MLH1 founder variant in Indian Lynch syndrome patient cohort. (PubMed, Fam Cancer)
    Here, we report a study of the missense variant c.306G > T in the MLH1 gene, the first potential founder variant identified in LS patients of Indian ethnicity. Haplotype analysis consisting of 25 LS carriers with the MLH1 c.306G > T variant and 100 healthy controls confirmed a shared haplotype in cases spanning a 27.8 kb region encompassing the c.306G > T variant (
    Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    2d
    Microsatellite instability and high tumor mutational burden detected by next generation sequencing are concordant with loss of mismatch repair proteins by immunohistochemistry. (PubMed, Cancer Genet)
    Genetic/epigenetic alterations in the MMR genes are an underlying reason for most positive findings. The association of MSH2/MSH6 loss with prostatic neoplasms is of in-terest, but sample size is limited, and further studies are warranted to address this association.
    Journal • Next-generation sequencing • Mismatch repair • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker • IO biomarker • Discordant
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    TMB-H • MSI-H/dMMR
    4d
    MesaCAPP: Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome (clinicaltrials.gov)
    P2, N=150, Recruiting, Ann-Sofie Backman | N=260 --> 150 | Trial completion date: Oct 2038 --> Sep 2045 | Trial primary completion date: Oct 2028 --> Sep 2032
    Enrollment change • Trial completion date • Trial primary completion date
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)
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    MSH2 mutation • MLH1 mutation
    4d
    Comprehensive Clinical Genetics, Molecular and Pathological Evaluation Efficiently Assist Diagnostics and Therapy Selection in Breast Cancer Patients with Hereditary Genetic Background. (PubMed, Int J Mol Sci)
    Further immunohistochemistry analysis of breast tumour tissues helped clarify the causative role of these variants. Comprehensive clinical and molecular genetic evaluation is beneficial for the diagnosis and management of patients with P/LP variants in hereditary tumour-predisposing genes and can serve as a basis for effective therapy selection, such as PARP inhibitors or immunotherapy.
    Retrospective data • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    5d
    Detection of Mismatch Repair Deficiency in Endometrial Cancer: Assessment of IHC, Fragment Length Analysis, and Amplicon Sequencing Based MSI Testing. (PubMed, Cancers (Basel))
    Furthermore, reduced MSI signal was observed in tumours with isolated MSH6 loss (p = 0.009 Ohio, p = 6.2 × 10-5 Manchester) and in both ECs and CRCs with germline defects, although this only reached significance in CRCs (p = 0.002). These results provide further evidence that ECs with MSH6 loss in particular and LS tumours in general have an attenuated MSI signal, providing support for current guidelines specifically recommending IHC for LS detection and immune checkpoint therapy assessment in EC.
    Journal • Mismatch repair • MSi-H Biomarker • IO biomarker
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    MSI (Microsatellite instability) • MSH6 (MutS homolog 6)
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    MSI-H/dMMR
    9d
    Prevalence and Distribution of Unexpected Actionable Germline Pathogenic Variants Identified on Broad-Based Multigene Panel Testing Among Patients With Cancer. (PubMed, JCO Precis Oncol)
    In patients with cancer, MGPT identified a rate of 1.7% PV in unexpected actionable cancer predisposition genes. Findings were more often unexpected (2.8%) when considering only the patient cancer history. These findings may justify consideration of broader MGPT panels in patients with cancer, given implications for subsequent surveillance, cascade testing, and treatment options dependent on specific findings.
    Retrospective data • Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MITF (Melanocyte Inducing Transcription Factor) • SDHC (Succinate Dehydrogenase Complex Subunit C) • HOXB13 (Homeobox B13) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
    11d
    Mismatch Repair Proficient Colorectal Adenocarcinoma in Two Patients With Lynch Syndrome. (PubMed, Clin Genet)
    While the MMRd/MSI carcinoma was recognized early and showed complete pathologic response after pembrolizumab treatment, the MMRp/MSS adenocarcinoma was underrecognized and poorly responsive to treatment. A second patient, with a pathogenic PMS2 variant, also developed a MMRp CRC. These cases highlight the complex biological pathways in CRC development and the impact of molecular classification on treatment.
    Journal • Mismatch repair • PD(L)-1 Biomarker • IO biomarker
    |
    MSI (Microsatellite instability) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2)
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    Keytruda (pembrolizumab)
    11d
    The novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma. (PubMed, Neuro Oncol)
    KL-50-based compounds are a promising new strategy for the treatment of MGMT-deficient, MMR-deficient GBM that recurs after frontline TMZ.
    Journal • Mismatch repair
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    MSH6 (MutS homolog 6)
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    MSI-H/dMMR
    |
    temozolomide
    11d
    Survival of Patients with Resected Microsatellite Instability-High, Mismatch Repair Deficient, and Lynch Syndrome-Associated Pancreatic Ductal Adenocarcinomas. (PubMed, Ann Surg Oncol)
    Before routine use of immune checkpoint inhibitors, the patients with MSI-H, MMRd, and LS-associated PDACs displayed significantly better survival than the patients with MSS, MMR-proficient, non-LS-associated PDACs. It is expected that survival for this cohort will further improve with increased availability of immunotherapy.
    Journal • Mismatch repair • Microsatellite instability • MSi-H Biomarker • IO biomarker
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR
    12d
    Evaluation of a combined model of Polygenic Risk Score and mismatch repair genes in the association of colorectal cancer for Norwegian cohort. (PubMed, Tumori)
    We also observed that the combined model of PRS and the status of MMR significantly improved the prediction performance. The findings suggest that a combined model of a PRS and the status of MMR genes improves the prediction performance of CRC in Norwegian data.
    Journal • Mismatch repair
    |
    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    16d
    Testing Immunotherapy (Atezolizumab) With or Without Chemotherapy in Locoregional MSI-H/dMMR Gastric and Gastroesophageal Junction (GEJ) Cancer (clinicaltrials.gov)
    P2, N=240, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSI-H/dMMR • MSH6 expression
    |
    Tecentriq (atezolizumab) • docetaxel • capecitabine • oxaliplatin • leucovorin calcium • fluorouracil topical
    17d
    Overview of a comparative analysis of microsatellite instability and standard mismatch repair protein-deficiency tests in a large cancer cohort. (PubMed, Pathologie (Heidelb))
    dMMR and MSI-high likely result in an increased rate of structurally altered proteins, i.e., neoantigens, and the efficacy of cancer immunotherapies is thus expected to be higher. We compared MMR IHC to MSI PCR in a large cohort of cancer patients to study how PCR test results correlate to MMR IHC. Our data imply that preanalytical factors strongly influence the results of MMR IHC and MSI PCR and may question the current dogma that dMMR phenotype and genetic MSI status are equivalent predictive markers for immunotherapies.
    Review • Journal • Mismatch repair • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker • IO biomarker
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    MSI-H/dMMR
    18d
    Mayo Clinic Tapestry Study: A Large-Scale Decentralized Whole Exome Sequencing Study for Clinical Practice, Research Discovery, and Genomic Education. (PubMed, Mayo Clin Proc)
    A large, decentralized, clinical Exome+ assay study in a tertiary medical center detects actionable germline variants, educates patients as well as providers, and offers access to big data for discovery that advances human health.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule) • APOB (Apolipoprotein B)
    19d
    Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer. (PubMed, BMC Cancer)
    Immunohistochemical analysis can identify prognostically different molecular subtypes of gastric cancer. The method is inexpensive and fast, yet reveals significant information for clinical decision-making. However, our study did not find that either molecular subtyping performed better than the other classification. Thus, further development of the most optimal grouping of different molecular subtypes is still needed.
    Journal
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1)
    |
    TP53 wild-type
    20d
    IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions. (PubMed, Sci Rep)
    Our study supports the hypothesis that metachronous RC can occur in a cancerization field in patients with weak systemic and local immune systems. The peculiar site of RC makes the mismatch-repair genes deficiency in metachronous cancer onset less relevant.
    Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule) • HLA-C (Major Histocompatibility Complex, Class I, C)
    23d
    Initiation of molecular testing of endometrial carcinomas in a population-based setting: practical considerations and pitfalls. (PubMed, Histopathology)
    This represents one of the first population-based studies investigating the prevalence of the different TCGA molecular groups of endometrial carcinomas in an unselected population. Performing molecular testing on biopsies enables management to be tailored to the molecular group and allows integration of the TCGA group into the report of the final resection specimen. We hope our experience will facilitate other laboratories in undertaking TCGA molecular classification.
    Journal
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    ER (Estrogen receptor) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    24d
    Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas. (PubMed, Head Neck Pathol)
    Microsatellite instability in oropharyngeal SCC is demonstrated by the association between loss of protein expression and its heterodimer imbalance with disease-free survival. It was demonstrated that the imbalance of the MMR complex can consequently lead to resistance to treatment and a decrease in disease-free survival in p16 + oropharyngeal SCC tumors.
    Journal • Mismatch repair
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    MSH6 expression
    24d
    Genomic Analysis of Advanced Phyllodes Tumors Using Next-Generation Sequencing and Their Chemotherapy Response: A Retrospective Study Using the C-CAT Database. (PubMed, Medicina (Kaunas))
    One patient with a high tumor mutational burden (37/Mb) responded to pembrolizumab... Our findings suggest distinct molecular patterns in phyllodes tumors compared to other soft tissue sarcomas, with potential implications for treatment selection. The identification of specific genetic alterations associated with treatment resistance may guide therapeutic decision-making, while the presence of actionable mutations in select cases indicates potential opportunities for targeted therapy approaches.
    Retrospective data • Journal • Next-generation sequencing • Tumor mutational burden • PD(L)-1 Biomarker • Metastases
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MSH6 (MutS homolog 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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    TP53 mutation • TMB-H
    |
    FoundationOne® CDx • OncoGuide™ NCC Oncopanel System
    |
    Keytruda (pembrolizumab)
    25d
    Prospective Screening of Cancer Syndromes in Patients with Mesenchymal Tumors. (PubMed, Cancers (Basel))
    We conclude that second-hit analyses can be used in standard of care to identify syndrome-related tumors. This approach can help distinguish true manifestations of tumor syndromes from unrelated germline findings and enhance the understanding of germline predisposition in soft tissue tumors. Prospective screening using germline whole genome sequencing should be considered when comprehensive somatic sequencing is introduced into clinical practice.
    Journal • IO biomarker
    |
    TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • CHEK2 (Checkpoint kinase 2) • KCNQ1OT1 (KCNQ1 Opposite Strand/Antisense Transcript 1) • SDHC (Succinate Dehydrogenase Complex Subunit C) • CDC73 (Cell Division Cycle 73)
    25d
    In silico splicing analysis of the PMS2 gene: exploring alternative molecular mechanisms in PMS2-associated Lynch syndrome. (PubMed, BMC Genom Data)
    Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA experiments. Additional functional data is necessary to validate our findings.
    Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule)
    26d
    Feasibility Study: IGNITE-TX (Identifying Individuals for Genetic Testing & Treatment) Intervention (clinicaltrials.gov)
    P=N/A, N=247, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=80 --> 247
    Enrollment closed • Enrollment change
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)
    |
    BRCA1 mutation • MSH2 mutation • PMS2 mutation
    1m
    IMMUNOREACT 8: Immune markers of local tumor spread in patients undergoing transanal excision for clinically N0 rectal cancer. (PubMed, Surgery)
    Our study showed that the association between the high proportion of epithelial cells acting as presenting cells and deep or lateral tumor spread may be explained by the presence of a greater tumor load at the site. Moreover, it showed that weak activation of CD8+ T cells within the rectal mucosa is associated with lateral tumor spread and eventually a higher recurrence rate. The mucosal level of CD8β infiltration detected at immunohistochemistry might be tested as a marker of lateral tumor spread and potentially translated into clinical practice.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD38 (CD38 Molecule) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2) • IL2RA (Interleukin 2 receptor, alpha) • FOXP3 (Forkhead Box P3) • CD40 (CD40 Molecule) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule) • ISG20 (Interferon Stimulated Exonuclease Gene 20)
    1m
    Multi-ethnic heterozygote frequencies of cancer susceptibility genes to inform counseling of reproductive risk. (PubMed, Genet Med)
    Heterozygote frequency estimates for AD CPGs that cause AR disease provides information to facilitate discussions regarding reproductive risk. Future studies are needed to assess whether utilization of these data will influence couples' reproductive risk planning.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
    1m
    Recurrent GRHL fusions in a subset of sebaceoma: microscopic and molecular characterisation of eight cases. (PubMed, Histopathology)
    In conclusion, we report recurrent fusions of the GRHL genes in a distinctive subset of sebaceomas harbouring infundibulocystic differentiation, a frequent organoid growth pattern and lack of mismatch repair deficiency.
    Journal
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    AR (Androgen receptor) • BCL6 (B-cell CLL/lymphoma 6) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • BCOR (BCL6 Corepressor) • TP63 (Tumor protein 63)
    |
    AR expression • MSH6 expression
    1m
    The impact of preoperative treatment on mismatch repair protein and HER2 expression in colorectal cancer: an analysis of paired samples. (PubMed, BMC Cancer)
    PT is associated with a reduction in MMR expression, notably for the MSH2 protein, while it does not appear to influence HER2 expression.
    Retrospective data • Journal • Mismatch repair
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    HER-2 (Human epidermal growth factor receptor 2) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    MSI-H/dMMR • HER-2 overexpression • HER-2 expression • MSH6 expression
    |
    5-fluorouracil • capecitabine
    1m
    Establishment and Validation of a Prognostic Nomogram for Predicting Postoperative Overall Survival in Advanced Stage III-IV Colorectal Cancer Patients. (PubMed, Cancer Med)
    We constructed and validated an original nomogram for predicting the postoperative OS of advanced stage CRC patients, which can help facilitates physicians to accurately assess the individual survival of postoperative patients and identify high-risk patients.
    Journal • Metastases
    |
    MSH6 (MutS homolog 6) • CA 19-9 (Cancer antigen 19-9)
    1m
    Advantages of next-generation sequencing (NGS) in the molecular classifi cation of endometrial carcinomas - our experience with 270 cases. (PubMed, Ceska Gynekol)
    In comparison with recommended diagnostic algorithms, NGS provides a more reliable classification of EC into particular molecular subgroups. Furthermore, NGS reveals the complex molecular genetic background in individual ECs, which is especially significant within ECs with no specific molecular profile. These data can serve as a springboard for the research of therapeutic programs committed to targeted therapy in this type of tumor.
    Journal • Next-generation sequencing • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • BCOR (BCL6 Corepressor) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • POLD1 (DNA Polymerase Delta 1)
    |
    TP53 mutation • PIK3CA mutation • PTEN mutation • POLE mutation
    1m
    The guidelines for clinical practice for carriers of germline mutations in the Lynch syndrome predisposition genes MLH1, MSH2, MSH6, PMS2 and large deletions of EPCAM (4.2024). (PubMed, Klin Onkol)
    The drafting of the guidelines was organized by the Oncogenetics Working Group of the Society for Medical Genetics and Genomics of J. E. Purkyně Czech Medical Society, in cooperation with representatives of oncology, oncogynecology, and gastroenterology. The guidelines are based on the current recommendations of the National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO) and take into account the capacity of the Czech healthcare system.
    Clinical guideline • Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule)
    |
    MSH2 mutation • PMS2 mutation • MSH6 deletion
    1m
    Germline mismatch repair gene mutations in children with tumors: a case series from two centers. (PubMed, Transl Pediatr)
    A better diagnostic approach is to perform genetic testing to rule out the risk as early as possible when a newborn presents with cafe-au-lait spots, which are a typical feature of hereditary syndromes. Therefore, it is important to use germline genetic testing, combined with clinical phenotypic observation, to establish a diagnosis of a cancer susceptibility syndrome caused by an MMR gene mutation.
    Journal • Mismatch repair
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    NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSH6 mutation • MSH2 mutation • MLH1 mutation
    1m
    Founder pathogenic variants in colorectal neoplasia susceptibility genes in Ashkenazi Jews undergoing colonoscopy. (PubMed, BJC Rep)
    Overall, we found that 10 to 15% of Ashkenazi Jewish persons undergoing colonoscopy harbor variants of interest in colorectal and/or polyposis predisposition. This includes pathogenic variants in MSH6, which is associated with colorectal cancer but not with polyposis. We identified no pathogenic variants in more recently discovered polyposis predisposition genes (POLE, POLD1 or NTHL1), rendering the presence of such founder variants rare.
    Journal
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    MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • POLD1 (DNA Polymerase Delta 1)
    1m
    Characteristics of Cancer in Subjects Carrying Lynch Syndrome-Associated Gene Variants in Taiwanese Population: A Hospital-Based Study in Taiwan. (PubMed, Cancers (Basel))
    The apparent under diagnosis of LS highlights the urgent need for enhanced surveillance and genetic counseling in this demographic. Our findings suggest that adjustments in the current screening protocols may be warranted to better identify and manage at-risk individuals.
    Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    1m
    Genomic alterations associated with early-stage disease and early recurrence in patients with colorectal cancer. (PubMed, Oncologist)
    Early-stage CRC patients can have distinct genomic profiles and CGP in this population can help expand access to targeted therapies.
    Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker
    |
    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • RNF43 (Ring Finger Protein 43)
    |
    BRAF V600E • MSI-H/dMMR • BRAF V600 • RNF43 mutation
    |
    FoundationOne® CDx
    1m
    Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers (clinicaltrials.gov)
    P2, N=35, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed
    Trial completion
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSI-H/dMMR
    |
    Keytruda (pembrolizumab)
    1m
    Radiation and TSR-042 (Dostarlimab) in People With Endometrial Cancer After They Receive Surgery (clinicaltrials.gov)
    P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Recruiting | N=31 --> 62 | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026
    Enrollment open • Enrollment change • Trial completion date • Trial primary completion date • Checkpoint inhibition • Mismatch repair • Surgery • Checkpoint block • Metastases
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    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSI-H/dMMR • POLE mutation
    |
    Jemperli (dostarlimab-gxly)
    1m
    Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov)
    P1/2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    BRAF mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
    |
    NOUS-209
    1m
    A Phase 1/2 Study to Evaluate the Safety and Efficacy of MK-2870 Monotherapy or in Combination With Other Anticancer Agents in Gastrointestinal Cancers (ChiCTR2400089007)
    P2, N=130, Not yet recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Union Hospital, Tongji Medical College, Huazhong University of
    New P2 trial • Combination therapy
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • CD4 (CD4 Molecule)
    |
    MSI-H/dMMR • BRCA mutation • MSH6 expression
    |
    FoundationOne® CDx
    |
    5-fluorouracil • sacituzumab tirumotecan (MK-2870)
    1m
    A Phase 2 Study of Mirvetuximab Soravtansine (IMGN853) and Pembrolizumab in Endometrial Cancer (EC) (clinicaltrials.gov)
    P2, N=18, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Aug 2028 --> May 2027 | Trial primary completion date: Aug 2025 --> Jun 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    FOLR1 ( Folate receptor alpha ) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSH6 expression
    |
    Keytruda (pembrolizumab) • Elahere (mirvetuximab soravtansine-gynx)
    1m
    Fecal Microbiota Transplant and Re-introduction of Anti-PD-1 Therapy (Pembrolizumab or Nivolumab) for the Treatment of Metastatic Colorectal Cancer in Anti-PD-1 Non-responders (clinicaltrials.gov)
    P2, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CEACAM5 (CEA Cell Adhesion Molecule 5)
    |
    MSI-H/dMMR
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab)
    1m
    Association Between the Protein Expressions of MutS Homologs and Villin and the Clinicopathological Characteristics in 310 Colon Cancer Patients (PubMed, Sichuan Da Xue Xue Bao Yi Xue Ban)
    The expressions of MSH2, MSH6, and villin are closely correlated with the pathological features of colon cancer patients. Evaluating the expression of the three proteins may assist in the clinical diagnosis, treatment, and prognosis evaluation of colon cancer.
    Journal
    |
    MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSH6 expression
    1m
    Current status of cancer genomic profiling (CGP) tests in brain tumor treatment - complementing brain tumor pathological diagnosis with CGP- (SNO 2024)
    Molecular diagnostics through CGP testing served as an aid in diagnosis according to WHO2021. Cases where drug suggestions were feasible underwent treatment with targeted molecular therapies and checkpoint inhibitor. We experienced cases where hereditary cancer syndromes such as Lynch syndrome were diagnosed through the detection of germline pathogenic variants.
    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MSH6 (MutS homolog 6)
    |
    BRAF V600E • TMB-H • BRAF V600 • IDH1 R132H • TERT mutation • IDH wild-type • IDH1 R132 • IDH mutation + BRAF V600E
    |
    FoundationOne® CDx • OncoGuide™ NCC Oncopanel System
    2ms
    PancreasScan: Pancreatic Cancer Screening for At-risk Individuals (clinicaltrials.gov)
    P=N/A, N=1395, Recruiting, Beth Israel Deaconess Medical Center | N=500 --> 1395 | Trial completion date: Mar 2028 --> Dec 2032 | Trial primary completion date: Mar 2027 --> Dec 2032
    Enrollment change • Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • EPCAM (Epithelial cell adhesion molecule) • PRSS1 (Serine Protease 1)
    |
    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CDKN2A mutation • MLH1 mutation • PMS2 mutation • BRCA mutation
    2ms
    High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome. (PubMed, Ann Gastroenterol Surg)
    Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20 y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively. Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC.
    Journal
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)